PMID- 12509430 OWN - NLM STAT- MEDLINE DCOM- 20030423 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 278 IP - 10 DP - 2003 Mar 7 TI - Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. PG - 8356-62 AB - The activation of heterotrimeric G proteins is accomplished primarily by the guanine nucleotide exchange activity of ligand-bound G protein-coupled receptors. The existence of nonreceptor guanine nucleotide exchange factors for G proteins has also been postulated. Yeast two-hybrid screens with Galpha(o) and Galpha(s) as baits were performed to identify binding partners of these proteins. Two mammalian homologs of the Caenorhabditis elegans protein Ric-8 were identified in these screens: Ric-8A (Ric-8/synembryn) and Ric-8B. Purification and biochemical characterization of recombinant Ric-8A revealed that it is a potent guanine nucleotide exchange factor for a subset of Galpha proteins including Galpha(q), Galpha(i1), and Galpha(o), but not Galpha(s). The mechanism of Ric-8A-mediated guanine nucleotide exchange was elucidated. Ric-8A interacts with GDP-bound Galpha proteins, stimulates release of GDP, and forms a stable nucleotide-free transition state complex with the Galpha protein; this complex dissociates upon binding of GTP to Galpha. FAU - Tall, Gregory G AU - Tall GG AD - Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75390-9041, USA. FAU - Krumins, Andrejs M AU - Krumins AM FAU - Gilman, Alfred G AU - Gilman AG LA - eng SI - GENBANK/AY177754 SI - GENBANK/AY177755 GR - GM34497/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20021230 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Nuclear Proteins) RN - 0 (Ric8a protein, rat) RN - 0 (Ric8b protein, rat) RN - EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins) SB - IM MH - Animals MH - Caenorhabditis elegans Proteins/*metabolism MH - Chromatography, Gel MH - Cloning, Molecular MH - *Guanine Nucleotide Exchange Factors MH - Heterotrimeric GTP-Binding Proteins/genetics/isolation & purification/*metabolism MH - Molecular Sequence Data MH - Nuclear Proteins/*metabolism MH - Rats MH - Two-Hybrid System Techniques EDAT- 2003/01/02 04:00 MHDA- 2003/04/24 05:00 CRDT- 2003/01/02 04:00 PHST- 2003/01/02 04:00 [pubmed] PHST- 2003/04/24 05:00 [medline] PHST- 2003/01/02 04:00 [entrez] AID - S0021-9258(20)86459-X [pii] AID - 10.1074/jbc.M211862200 [doi] PST - ppublish SO - J Biol Chem. 2003 Mar 7;278(10):8356-62. doi: 10.1074/jbc.M211862200. Epub 2002 Dec 30.